By Counterforce Health Team —

Givlaari: A Treatment for Acute Hepatic Porphyria

Living with acute hepatic porphyria (AHP) can be unpredictable and painful. People with this rare genetic disorder often experience sudden, severe attacks that affect the nervous system and other parts of the body. Until recently, treatments focused mainly on managing symptoms and preventing triggers.

Then came Givlaari® (givosiran) — a groundbreaking therapy designed to treat AHP at its genetic root. Approved by the U.S. Food and Drug Administration (FDA) in 2019, Givlaari is one of the first RNA-based medicines to specifically target the underlying cause of this condition.

What Is Givlaari?

Givlaari (givosiran) is a prescription medication used to treat adults with acute hepatic porphyria (AHP).

AHP refers to a group of rare inherited disorders of the liver that cause the body to build up toxic substances involved in heme production — a process essential for carrying oxygen in the blood.

By reducing the buildup of these toxic compounds, Givlaari helps prevent or lessen the frequency and severity of porphyria attacks.

Understanding Acute Hepatic Porphyria

AHP occurs when there is a defect in one of the enzymes needed to make heme — a key component of hemoglobin. When the enzyme doesn’t work properly, porphyrin precursors (such as aminolevulinic acid [ALA] and porphobilinogen [PBG]) accumulate in the body, leading to attacks and chronic symptoms.

Common symptoms of AHP include:

  • Severe abdominal pain
  • Muscle weakness
  • Nausea and vomiting
  • Seizures
  • Dark or reddish urine
  • Fatigue
  • Anxiety or confusion

Triggers can include certain medications, hormonal changes, fasting, alcohol, or stress. Because attacks can be life-threatening, quick treatment and prevention are crucial.

How Givlaari Works

Givlaari is based on a technology called RNA interference (RNAi) — a natural process in the body that “silences” or reduces the activity of specific genes.

Here’s how it helps people with AHP:

  1. Givlaari contains givosiran, a small interfering RNA (siRNA) molecule.
  2. It targets and blocks the liver gene that makes aminolevulinic acid synthase 1 (ALAS1) — the enzyme responsible for the buildup of toxic precursors in AHP.
  3. By lowering ALAS1 activity, Givlaari reduces the production of ALA and PBG, the substances that trigger attacks.
  4. As a result, patients experience fewer and less severe porphyria attacks and may notice improvement in chronic symptoms such as pain and fatigue.

This approach addresses the underlying cause of AHP, not just the symptoms.

How Givlaari Is Given

  • Administration: Givlaari is given as a subcutaneous injection (under the skin) by a healthcare professional.
  • Frequency: Once every month (every 4 weeks).
  • Dose: The typical recommended dose is 2.5 mg per kilogram of body weight.
  • Location: Common injection sites include the abdomen, upper arm, or thigh.

Each treatment visit is relatively quick, and most patients tolerate the injections well.

Clinical Evidence

Givlaari’s approval was based on results from the ENVISION Phase 3 clinical trial, which studied adults with AHP.

Key results:

  • Patients receiving Givlaari experienced a 74% reduction in the average number of porphyria attacks compared to those given a placebo.
  • Many participants had fewer hospitalizations, emergency visits, and hemin infusions.
  • Levels of toxic precursors (ALA and PBG) dropped significantly within days of treatment.

In addition to reducing attack frequency, patients often reported improved energy levels, better daily functioning, and less pain between attacks.

Benefits of Givlaari

Givlaari has transformed the management of AHP by offering both preventive and long-term benefits:

  • Fewer acute porphyria attacks
  • Reduced need for hospitalizations and hemin therapy
  • Lower buildup of toxic porphyrin precursors
  • Improved quality of life and daily functioning
  • Ongoing control of chronic symptoms in some patients

Because it directly targets the genetic mechanism behind AHP, Givlaari provides a disease-modifying effect — something no previous therapy could do.

Possible Side Effects

Like all medications, Givlaari can cause side effects. The most common include:

  • Nausea
  • Fatigue
  • Injection-site reactions (redness, pain, itching, or swelling)
  • Elevated liver enzymes (ALT, AST)
  • Decreased kidney function (mild to moderate)

Less common but important precautions:

  • Liver monitoring: Blood tests are performed regularly to check for changes in liver function.
  • Kidney function tests: Monitored in patients with existing renal impairment.
  • Allergic reactions: Rare, but any swelling, difficulty breathing, or rash should be reported immediately.

Patients are encouraged to keep an open line of communication with their healthcare team throughout treatment.

Who Can Receive Givlaari

Givlaari is approved for adults with acute hepatic porphyria, including subtypes such as:

  • Acute intermittent porphyria (AIP)
  • Variegate porphyria (VP)
  • Hereditary coproporphyria (HCP)
  • ALA dehydratase–deficient porphyria (ALAD deficiency)

It is not currently approved for children or for other types of porphyria that do not cause acute attacks.

Monitoring and Follow-Up

Because Givlaari affects liver metabolism, patients typically undergo routine monitoring that includes:

  • Liver enzyme tests before and during treatment
  • Kidney function tests
  • Blood levels of ALA and PBG to track disease activity
  • Regular reviews of attack frequency and symptom control

This monitoring helps ensure the medication remains effective and safe over time.

Practical Considerations

  • Storage: Givlaari is stored refrigerated by healthcare professionals and prepared prior to injection.
  • Scheduling: Monthly appointments are required; consistent timing is important for effectiveness.
  • Lifestyle: Patients should continue avoiding known triggers, such as fasting, certain drugs, and alcohol.
  • Support: The manufacturer and rare disease foundations offer patient assistance programs and educational resources for people living with AHP.

The Bottom Line

Givlaari (givosiran) represents a new era in the treatment of acute hepatic porphyria. By using RNA interference to reduce the production of harmful substances in the liver, it helps prevent attacks and improves quality of life for those living with this debilitating disease.

While it requires ongoing monitoring and monthly injections, many patients experience dramatic reductions in attacks and regain a sense of control over their health.

For individuals affected by AHP, Givlaari offers not just treatment — but renewed hope.